Abstract Atrial fibrillation is the most common significant cardiac arrhythmia and is associated with a five-fold increased risk of stroke from thromboembolism. Over 94% of these emboli arise from the left atrial appendage. Systemic embolic phenomena are rare, accounting for less than 1 out of 10 of all embolic events, but have a similar prevention strategy. Anticoagulation significantly reduces the risk of these events, and thus forms the cornerstone of therapy for most patients with atrial fibrillation. Left atrial appendage occlusion with the Watchman device is a recently approved alternative for stroke prevention in selected patients. We present a case of an active duty U.S. Navy sailor at low risk for thromboembolism who nonetheless suffered recurrent thromboembolic events despite appropriate anticoagulation, and thus underwent Watchman implantation. The therapy in this case will ideally provide a lifetime of protection from recurrent systemic embolization while allowing the patient to continue his active duty military career without restriction due to oral anticoagulation. INTRODUCTION Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting up to six million Americans.1 The presence of AF confers significant morbidity and mortality, including a five-fold increased risk of stroke or transient ischemic attack.2 In patients with AF, it is estimated that over 94% of cardiogenic emboli arise from thrombi formed in the left atrial appendage (LAA).3 Anticoagulation prevents thrombus formation and thus reduces the risk of embolization by approximately 64%, so is recommended for patients with an elevated stroke risk.2 In 2015, the U.S. Food and Drug Administration (FDA) approved the Watchman Left Atrial Appendage Closure Device (Boston Scientific, Natick, Massachusetts) as an alternative to long-term anticoagulation in select patients with a high risk of stroke. Here we present a 39-yr-old active duty U.S. Navy sailor with non-valvular AF who suffered recurrent thromboembolic events despite appropriate use of oral anticoagulation, who was ultimately treated with the Watchman device. This is an uncommon scenario with no clinical trial data to guide decision-making, but this approach presents unique advantages, especially for active duty service members. CASE PRESENTATION A 39-yr-old active duty male U.S. Navy sailor presented to the Emergency Department with less than 24 h of palpitations. He recalled two prior episodes which each lasted less than 2 h. ECG demonstrated AF (Fig. 1). Transthoracic echocardiogram demonstrated mild concentric left ventricular hypertrophy, normal bi-ventricular systolic function, and normal valve function. His CHA2DS2-VASc score was zero, so he underwent pharmacologic cardioversion with flecainide and was discharged home. Ten days later he represented with a painful left index finger. Examination demonstrated diminished left radial and ulnar pulses and a cold hand. Urgent angiography revealed emboli in the left radial, ulnar, and interosseous arteries (Fig. 2). Treatment with intra-arterial tPA and heparin restored antegrade and his symptoms resolved over the next 24 h. Brain MRI demonstrated no evidence of cerebral emboli, and he was started on rivaroxaban, flecainide, and metoprolol for long-term treatment and secondary prevention. FIGURE 1. View largeDownload slide ECG from the patient’s initial presentation, demonstrating rate controlled AF with left ventricular hypertrophy and repolarization abnormality. FIGURE 1. View largeDownload slide ECG from the patient’s initial presentation, demonstrating rate controlled AF with left ventricular hypertrophy and repolarization abnormality. FIGURE 2. View largeDownload slide Left arm angiogram demonstrating occlusion of the radial, ulnar, and interosseous arteries by multiple emboli. FIGURE 2. View largeDownload slide Left arm angiogram demonstrating occlusion of the radial, ulnar, and interosseous arteries by multiple emboli. Three years later, he awoke with severe flank pain, and again presented to the Emergency Department. Initial evaluation demonstrated new hypertension and an abdominal CT showed complete occlusion of the right renal artery (Fig. 3). Transesophageal echocardiogram demonstrated no cardiac thrombi and an intact atrial septum. Adherence with anticoagulation was verified, and an extensive evaluation for a hypercoagulable disorder was unremarkable. A multidisciplinary heart team (consisting of several general cardiologists, interventionalists, and electrophysiologists) concluded that this recurrent thromboembolism represented a failure of anticoagulation and recommended percutaneous LAA occlusion with the Watchman device (Fig. 4). Continuation of anticoagulation after LAA occlusion was considered as a “belt and suspenders” approach, but was decided against after carefully weighing the long-term risk of anticoagulation. FIGURE 3. View largeDownload slide Contrast CT demonstrating occlusion of the right renal artery (arrow) with resultant hypo-perfusion of the renal cortex. FIGURE 3. View largeDownload slide Contrast CT demonstrating occlusion of the right renal artery (arrow) with resultant hypo-perfusion of the renal cortex. FIGURE 4. View largeDownload slide Intra-procedural imaging from the Watchman implantation. (A) Pre-implantation transesophageal imaging of the LAA demonstrating no evidence of thrombus; (B) LAA angiography in left anterior-oblique-caudal projection demonstrating a large ‘chicken wing’ shaped appendage; (C) fluoroscopy of the Watchman after deployment at the orifice of the LAA; (D) one of four measurements of deployed device confirming position, compression, and absence of flow. FIGURE 4. View largeDownload slide Intra-procedural imaging from the Watchman implantation. (A) Pre-implantation transesophageal imaging of the LAA demonstrating no evidence of thrombus; (B) LAA angiography in left anterior-oblique-caudal projection demonstrating a large ‘chicken wing’ shaped appendage; (C) fluoroscopy of the Watchman after deployment at the orifice of the LAA; (D) one of four measurements of deployed device confirming position, compression, and absence of flow. DISCUSSION AF is the most common serious cardiac arrhythmia, affecting up to six million Americans, and is associated with a five-fold increased risk of stroke.1 Extracranial, or systemic, embolic events are less common. In one review of 37,973 patients from four large anticoagulation trials, systemic emboli accounted for only 10% of thromboembolic events, but were just as fatal as stroke, with a 30-day mortality of 24%.4 The most widely used method of quantifying the risk of stroke is the CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 yr, diabetes, prior stroke or transient ischemic attack, vascular disease, age 65–74 yr, and female sex category). In this scheme, higher scores indicate a greater stroke risk, and both age ≥75 and prior stroke or transient ischemic attack are given two points.2 This patient’s CHA2DS2-VASc score was zero on initial presentation, so no anticoagulation was prescribed after pharmacologic cardioversion. This is in accordance with AF guidelines, which state that anticoagulation or no antithrombotic may be considered for cardioversion in patients with AF or atrial flutter of less than 48-h duration.2 Moreover, in a retrospective study of 484 patients with less than 48 h of AF who underwent cardioversion, there were no thromboembolic events in those with CHA2DS2-VASc scores less than two.5 A similar study found a very low event rate in those without diabetes or heart failure.6 Despite low predicted risk, this patient experienced multiple systemic embolic events; first occlusion of multiple arteries in the left arm off anticoagulation, and later occlusion of the right renal artery despite anticoagulation with rivaroxaban. Rates of thromboembolism in patients on rivaroxaban are very low; in one trial of AF patients with an average CHA2DS2-VASc score of 3.5 there were only 1.7 strokes per 100 patient years.7 When such breakthrough thromboembolic events occur, non-adherence should be considered. Rivaroxaban must be taken every day without interruptions, and with the evening meal, as it has 34% lower bioavailability when taken without food.8 For this patient, interviews and review of prescription records verified appropriate anticoagulation use and adherence, so this was considered a failure of anticoagulation. The optimal management after such breakthrough events is unclear. The following strategies have been proposed; dose escalation, switching to an alternative anticoagulant, adding an antiplatelet agent, and non-pharmacologic treatment via LAA occlusion.9 Evidence for dose escalation comes primarily from the RE-LY trial and the direct thrombin inhibitor oral anticoagulant dabigatran.10 In contrast, rivaroxaban efficacy did not correlate with dose in the phase II trials that influenced dose selection in AF treatment.11,12 Changing to an alternative anticoagulant has unknown efficacy, as there have been no trials of this method or head-to-head comparisons between direct oral anticoagulants. The addition of an antiplatelet agent to anticoagulation has also been advocated, but may not reduce the risk of thromboembolism and significantly increases the risk of bleeding.13 LAA occlusion with the Watchman device has recently emerged as another option for the prevention of thromboembolism in selected patients with AF. The implant is composed of a nitinol frame and a permeable polyester fabric over the atrial cap. Small fixation barbs hold it in the LAA, and endothelialization gradually covers the device and seals nthe appendage. The Watchman device received FDA approval in 2015 for AF patients at risk for stroke who are suitable for short term anticoagulation but have an appropriate rationale to seek a non-pharmacologic alternative to warfarin. Compared with warfarin, the Watchman device is noninferior for the prevention of stroke in at-risk patients with AF, and is associated with a significant reduction in bleeding.14 Its efficacy in patients with failure of direct oral anticoagulants such as rivaroxaban has not been studied. Given this patient’s young age and failure of oral anticoagulation with rivaroxaban, the Watchman Device represented attractive option. Although unproven for this indication, it would prevent the patient from experiencing the cumulative risk of indefinite anticoagulation. One additional consideration for this patient was his preference remain on active duty and fully deployable worldwide. Chronic anticoagulation therapy, because of increased bleeding, typically is cause for referral to the physical evaluation board.15 For this patient and other active duty service members with AF, non-pharmacologic prophylaxis of thromboembolism with the Watchman device thus represents an attractive alternative that may be considered on an individual basis. CONCLUSION This case demonstrates the rare occurrence of thrombo-embolization in a low risk patient and breakthrough systemic embolization despite appropriate adherence with rivaroxaban anticoagulation. It emphasizes how low risk does not equal no risk, and illustrates how LAA occlusion with the Watchman device may be considered in young patients with oral anticoagulation treatment failure. Finally, it introduces some unique considerations for active duty military members with AF who wish to remain on active duty. 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Circulation 2013; 128( 22 SUPPL. 1): 796– 803. 5 Garg A, Khunger M, Seicean S, Chung MK, Tchou PJ: Incidence of thromboembolic complications within 30 days of electrical cardioversion performed within 48 hours of atrial fibrillation onset. JACC Clin Electrophysiol 2016; 2( 4): 487– 94. Google Scholar CrossRef Search ADS PubMed 6 Airaksinen KEJ, Grönberg T, Nuotio I, et al. : Thromboembolic complications after cardioversion of acute atrial fibrillation. J Am Coll Cardiol 2013; 62( 13): 1187– 92. Google Scholar CrossRef Search ADS PubMed 7 Patel M, Mahaffey K, Garg J: Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365( 10): 883– 91. Google Scholar CrossRef Search ADS PubMed 8 Trujillo T, Dobesh PP: Clinical use of rivaroxaban: pharmacokinetic and pharmacodynamic rationale for dosing regimens in different indications. Drugs 2014; 74( 14): 1587– 603. Google Scholar CrossRef Search ADS PubMed 9 Kazmi RS, Lwaleed BA: New anticoagulants: how to deal with treatment failure and bleeding complications. Br J Clin Pharmacol 2011; 72( 4): 593– 603. Google Scholar CrossRef Search ADS PubMed 10 Connolly SJ, Ezekowitz MD, Yusuf S, et al. : Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009; 361( 12): 1139– 51. Google Scholar CrossRef Search ADS PubMed 11 Turpie AG, Fisher WD, Bauer KA, et al. : BAY 59-7939: an oral, direct factor Xa inhibitor for the prevention of venous thromboembolism in patients after total knee replacement. A phase II dose-ranging study. J Thromb Haemost 2005; 3( 11): 2479– 86. Google Scholar CrossRef Search ADS PubMed 12 Eriksson BI, Borris LC, Dahl OE, et al. : Dose-escalation study of rivaroxaban (BAY 59-7939) – an oral, direct Factor Xa inhibitor – for the prevention of venous thromboembolism in patients undergoing total hip replacement. Thromb Res 2007; 120( 5): 685– 93. Google Scholar CrossRef Search ADS PubMed 13 Lamberts M, Gislason GH, Lip GYH, et al. : Antiplatelet therapy for stable coronary artery disease in atrial fibrillation patients taking an oral anticoagulant: a nationwide cohort study. Circulation 2014; 129( 15): 1577– 85. Google Scholar CrossRef Search ADS PubMed 14 Reddy VY, Sievert H, Halperin J, et al. : Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation a randomized clinical trial. JAMA 2014; 312( 19): 1988– 98. Google Scholar CrossRef Search ADS PubMed 15 Navas WA. SECNAV INSTRUCTION 1850.4E. Washington, DC, United States of America; 2002. Available at https://doni.documentservices.dla.mil/allinstructions.aspx; accessed February 19, 2018. Author notes The views expressed are solely those of the authors and do not reflect the official policy or position of the U.S. Army, U.S. Navy, U.S. Air Force, the Department of Defense, or the U.S. Government Published by Oxford University Press on behalf of Association of Military Surgeons of the United States 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Military Medicine – Oxford University Press
Published: May 23, 2018
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